Increased Risk of Non-alcoholic Fatty Liver Disease in Low Birth Weight Individuals

Recruiting

• Conditions: Low Birth Weight; Non-Alcoholic Fatty Liver Disease

• Registration Number: NCT05890365
• Lead Sponsor: Steno Diabetes Center Copenhagen

Brief Summary

The investigators recently demonstrated a increase in liver fat in early middle-aged LBW compared to normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). Here the investigators will further examine the Increased risk of non-alcoholic fatty liver disease in low birth weight individuals by performing a validation study.

Detailed Description

An adverse fetal environment characterized by low birth weight (LBW) plays a key role in the development of type 2 diabetes (T2D). The investigators recently demonstrated a 3-fold increase in liver fat in 26 early middle-aged LBW compared to 22 normal birth weight (NBW) men, and 20% of the LBW - but none of the normal birth weight (NBW) - men had previously unknown non-alcoholic fatty liver disease (NAFLD). The investigators hypothesize that ectopic fat deposition and NAFLD is among the earliest disease manifestations and on the critical path to the development of more severe cardiometabolic disease in LBW. Here we aim to perform an extended nested case-control screening study to evaluate hepatic steatosis (NAFLD) and fibrosis in early middle-aged, non-obese LBW men and women and NBW controls. In total, 250 LBW men and women (birth weight (BW) \<10% of the population) and 50 NBW controls (BW between 50-90% of the population) born at term (weeks 39-41), 35-40 years-of-age will be recruited from the National Danish Birth Registry for the nested case-control NAFLD screening study. The nested case-control NAFLD screening study will serve as a recruitment platform for a subsequent intervention study.

Study Timeline

• Study First Submitted: 2023-03-02
• Study First Submitted QC: 2023-05-26
• Study First Posted: 2023-06-06
• Study Start: 2023-12-14
• Status Verified: 2024-04
• Last Update Submitted: 2025-01-30
• Last Update Posted: 2025-02-03
• Primary Completion: 2025-08
• Study Completion: 2025-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• 250 healthy, men and women born with a low birth weight (birth weight (BW) <10% of the population) and 50 born with a normal birth weight controls (BW between 50-90% of the population)
• born at term (weeks 39-41)

Exclusion Criteria

• BMI>35 kg/m2
• Disease/medication known to affect primary outcome
• Self-reported high physical activity level
• Alcohol intake above general recommendations.
• Metabolic/liver disease
• Weight gain/loss of >3 kg within the past 6 months

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Liver fat content	0 minutes	Liver elastography (FibroScan) and validation by MRS

Secondary Outcome Measures

Name	Time	Method
Fasting insulin/C-peptide	0 minutes	pmol/l
Liver fibrosis	0 minutes	Liver elastography, validation by MR and liver histology
Fasting glucose	0 minutes	mmol/l
Fasting liver enzymes	0 minutes	U/L
Body composition	0 minutes	DEXA
Fasting lipids	0 minutes	mmol/l

Trial Locations

Locations (1)

Steno Diabetes Center Copenhagen; 🇩🇰 Herlev, Denmark